Bacteriophages in Generalized Infections: A Review of Global Experience and Prospects for Phage Therapy
Abstract
INTRODUCTION. Generalized infections and rising antimicrobial resistance necessitate the search for alternative therapeutic strategies, one of which is phage therapy. However, two fundamentally different models of its use for sepsis and bacteremia have emerged globally. A critical comparison of these models will help identify potential future directions for phage therapy in Russia. A IM. The aim of this study was to identify, based on a comparative analysis of clinical-pharmacological and regulatory models for bacteriophage use in the Russian Federation and internationally, key barriers limiting the use of phage therapy for generalized infections, and to determine priority areas for expanding the use of phage therapy for these conditions in Russia.
Discussion
A review of scientific publications in the MEDLINE and eLIBRARY.RU databases (up to December 2025), data from the State Register of Medicines of the Russian Federation, the international registry ClinicalTrials.gov, and regulatory documents was conducted. It was shown that in the United States and Europe phage therapy is implemented mainly in the form of personalized highly purified preparations for intravenous administration within the framework of “expanded access” programs. Successful clinical cases in infectious processes caused by Acinetobacter baumannii , Enterococcus faecium , and Staphylococcus aureus demonstrate the potential of the method. At the same time, its critical limitations have been identified: the impossibility of use for acute sepsis due to the lengthy period of cocktail selection (28–386 days); inefficiency due to titer instability (which led to the termination of the PhagoBurn study) and immune neutralization of bacteriophages. In the Russian Federation, 14 commercial bacteriophage preparations are registered, 11 of which are officially approved for use in generalized infections, but their use is only permitted orally, topically, and rectally; parenteral administration is not provided for by regulations. Individual selection of phage cocktails is not permitted by law; there are no “expanded access” mechanisms; no specialized randomized trials have been conducted in Russia. A comparative analysis identified the main barriers limiting the use of phage therapy: regulatory (the registration system requires new randomized clinical trials for any change in composition) and technological (lack of highly purified forms for intravenous administration, titer instability).
Conclusions
To expand the clinical use of bacteriophages for generalized infections in the Russian Federation, the following areas are proposed: development of highly purified forms for intravenous administration (and/or demonstration of the efficacy of the oral route in large studies), regulation of procedures for personalized selection of cocktails for a patient-specific isolate, and adaptation of the regulatory framework for the rapid modification and registration of bacteriophage cocktail compositions.